The principal goal of this project is to establish a correlate of broad protective immunity in a HIV-1/HIV-2 cross-protection model in rhesus macaques. This goal stems from our earlier work showing that macaques can be protected against infection with HIV-2 by immunization with HIV-1 antigens using HIV-1 recombinant pox-viruses for priming and HIV-1 soluble subunit proteins for boosting. Given that neither CTLs nor neutralizing antibodies correlated with protection in our model, other effector mechanisms appear to be responsible for protective immunity. In support of this idea, one recent study in a SIV model reported that protection correlated with enhanced release of anti-viral chemokines. Thus, the principal hypothesis of this project is that virus suppressive factors (VSF), comprised of virus inhibitory beta-chemokines (RANTES, MIP-1alpha, MIP-1beta) will be correlates of protective immunity in this model. This hypothesis will be tested in the first two specific aims. The secondary hypothesis of this project is to re-examine other correlates of protein in this model including serum antibody responses and, cell specimens permitting, CTLs. This goal is described in the third specific aim.